Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloropicrin (CCl3NO2) is a widely used soil fumigant with an unknown mechanism of acute toxicity. We investigated the possible involvement of dechlorination in CCl3NO2 toxicity by considering its metabolism, inhibition of pyruvate and succinate dehydrogenases, cytotoxicity in cultured cells, and interaction with hemoproteins. In a newly discovered pathway, CCl3NO2 is metabolized to thiophosgene, which is characterized as the cyclic cysteine adduct (raphanusamic acid) in the urine of mice. CCl3NO2 inhibits porcine heart pyruvate dehydrogenase complex (IC-50 4 microM) and mouse liver succinate dehydrogenase complex (IC-50 13 microM), whereas its dehalogenated metabolites (CHCl2NO2 and CH2ClNO2) are more than 10 times less effective. The inhibitory potency of CCl3NO2 for these dehydrogenase complexes is similar to that of captan, folpet, and dichlone fungicides (IC-50 2-6 microM). CCl3NO2 cytotoxicity with Hepa 1c1c7+ mouse hepatoma cells (IC-50 9 microM) is not correlated with glutathione depletion. Mice treated intraperitoneally with CCl3NO2 at 50 mg/kg but not with an equivalent dose of CHCl2NO2 show increased concentrations of oxyhemoglobin in liver. The acute toxicity of CCl3NO2 in mice is due to the parent compound or metabolites other than CHCl2NO2 or CH2ClNO2 and may be associated with inhibition of the pyruvate dehydrogenase complex and elevated oxyhemoglobin.
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PMID:Chloropicrin dechlorination in relation to toxic action. 1056 Oct 79